This project is focused on the determination of the CTG triplet repeat expansions in the cardiac specific genes, and investigation of their instability during aging and cardia pathology. Clinical phenotype in majority of cardiac disorders becomes more severe with age. This phenomenon could be associated with increase of triplet repeat expansions during aging. Therefore, we hypothesize that some cardiac genes bear triplet repeats that become expanded in disease and/or aging. By analogy with other neurological and muscular disorders, triplet repeats in cardiac genes could be a source of instability in the aged and sick heart. In Specific aim 1, we will search for triplet repeat containing genes in cardiac tissue. Cardiac cDNA libraries will be screened with triplet repeat-specific probes, and positive cDNAs will be analyzed by sequencing. In Specific aim 2, we will investigate whether triplet repeats in the isolated cardiac specific genes are polymorphic in patients with cardiac disorders, as well in normal controls of different age. These studies will be a first step in the understanding of triplet repeats instability in heart. Identification of expanded repeats in cardiac genes and analysis of their expression during aging and in disease will allow to determine the genetic component in sick and aged heart that potentially will help to develop therapy to prevent heart disease and heart aging.